We will investigate the regulation of tyrosine synthesis in hepatoma cells growing in culture. Both metabolic control (involving substrate and product levels, membrane transport properties) and genetic control (involving effects on protein synthesis and degradation) of the rate of hydroxylation of phenylalanine will be examined. The mechanisms of regulation of phenylalanine hydroxylase by cell population density and by hormones will be studied in detail. Primary rat hepatocytes and hepatoma cells will be examined, both for insight into the regulatory process and into differences between the normal and transformed cells. BIBLIOGRAPHIC REFERENCES: Koontz, W.A. and R. Shiman, Beef Kidney 3-Hydroxyanthanilic Acid Oxygenase, J. Biol. Chem., 251, 368 (1976). McClure, D., M. Miller and R. Shiman, Cell Density Dependent Regulation of Phenylalanine Hydroxylase Activity in Hepatoma Cells, Exptl. Cell Res. 98, 223 (1976).